biostudies-literatureLiu JWelch FoundationNational Institute of General Medical SciencesNIGMS NIH HHS5247-5256https://www.ebi.ac.uk/biostudies/studies/S-EPMC6124307biostudies-literatureUnknown57(35)GW182 and argonaute 2 (AGO2) are core proteins of the RNA interference complex. GW182 is a scaffolding protein that physically associates with AGO2 and bridges its interactions with other proteins. A fundamental problem in biology is how scaffolding proteins adapt or contribute to differing functional demands within cells. Here we test the necessity for human GW182 proteins (paralogs TNRC6A, TNRC6B, and TNRC6C) for several mechanisms of small duplex RNA-mediated control of gene expression, including translational silencing by miRNAs, translational silencing by siRNAs, transcriptional silencing, transcriptional activation, and splicing. We find that GW182 is required for transcriptional activation and for the activity of miRNAs but is dispensable for the regulation of splicing, transcriptioBiochemistryThe Requirement for GW182 Scaffolding Protein Depends on Whether Argonaute Is Mediating Translation, Transcription, or Splicing.PMC6124307GM R35 118103I-1244R35 GM118103Liu JLiu ZCorey DRfalseThe Requirement for GW182 Scaffolding Protein Depends on Whether Argonaute Is Mediating Translation, Transcription, or Splicing.GW182 and argonaute 2 (AGO2) are core proteins of the RNA interference complex. GW182 is a scaffolding protein that physically associates with AGO2 and bridges its interactions with other proteins. A fundamental problem in biology is how scaffolding proteins adapt or contribute to differing functional demands within cells. Here we test the necessity for human GW182 proteins (paralogs TNRC6A, TNRC6B, and TNRC6C) for several mechanisms of small duplex RNA-mediated control of gene expression, including translational silencing by miRNAs, translational silencing by siRNAs, transcriptional silencing, transcriptional activation, and splicing. We find that GW182 is required for transcriptional activation and for the activity of miRNAs but is dispensable for the regulation of splicing, transcriptio2018-01-01T00:00:00Z2018 Sep2025-04-19T10:57:44.199Z2019-09-07T07:00:14ZS-EPMC61243073008623810.1021/acs.biochem.8b00602